A study of the metabolism of the branched-chain amino acids has revealed a pathway of metabolism of leucine that is catabolic in bacteria and appears to be synthetic in humans. The pathway depends upon the activity of the enzyme leucine 2,3-aminomutase, which requires adenosylcobalamin as a cofactor. Another enzyme which functions in the pathway is beta-leucine transaminase; this enzyme has been partially purified. The relationship between enzyme activity and various disease states such as pernicious anemia and maple syrup urine disease will be examined.